The general objective is to utilize genetic markers to investigate the etiology and pathogenesis of human tumors. The primary approach involves determining the number of cells from which neoplasms arise, thereby providing important clues to their mode of origin. For example, a tumor that results from a rare event, like "spontaneous" somatic mutation, would be expected to arise in a single cell. Multicellular origin might be anticipated for a tumor caused by cell-to-cell spread of a virus. This problem can be investigated in subjects with at least two genetically distinct types of cells. Tumors with clonal origin should contain only one cell type whereas both types would be more likely in neoplasms arising in several cells. X-inactivation cellular mosaicism in females heterozygous for the glucose-6-phosphate dehydrogenase (G-6-PD) locus will be studied. The investigations will provide data relevant to the following questions which have important basic and therapeutic implications: 1. Does recurrence of lymphoma after long-term remission result from re-emergence of the original malignant cell line or from a "new" induction of neoplasia? 2. Does the pathogenesis of the acute leukemias involve recruitment of normal hematopoietic cells or do the diseases result from altered clones? 3. Are there any normal stem cells in chronic myelocytic leukemia (CML) and, if so, what method can be used to favor their growth over the neoplastic cells? 4. Do the acute leukemias which develop in the course of hematopoietic clonal neoplasms such as CML, polycythemia vera, myelofibrosis, multiple myeloma, etc., involve the pre-existing neoplastic clones or do they result from "new" malignant transformations? 5. Does the pathogenesis of carcinoma involve the occurrence in the same cell of two or more mutation-like events and/or does it involve recruitment of normal cells? 6. Do metastases originate from one or from many primary tumor cells? 7. Do tumors which occur in syndromes clearly inherited by mendelian mechanisms have multicellular origin? 8. Do tumors caused by strong environmental influences such as viruses have multicellular origin?